The transmissible spongiform encephalopathies (TSEs or prion diseases)are fatal untreatable neurodegenerative diseases such as scrapie, Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy and chronic wasting disease (CWD). TSE pathogenesis involves the accumulation of an abnormal misfolded protein, called PrPres, in infected hosts. In FY 2013: 1) We have collaborated with extramural investigators to identify a designed Trpzip-3 β-hairpin that inhibits amyloid formation in two different amyloid systems. 2) We have continued to search for new anti-prion compounds from libraries of novel compounds that have been synthesized in Brazil by our collaborators. A number of new compounds have been identified that block PrP-res formation and have other attractive characteristics, but further testing of these compounds will be required to better establish their therapeutic potential.

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Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2013
Total Cost
$131,208
Indirect Cost
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Ferreira, Natalia C; Marques, Icaro A; Conceicao, Wesley A et al. (2014) Anti-prion activity of a panel of aromatic chemical compounds: in vitro and in silico approaches. PLoS One 9:e84531
Vieira, Tuane C R G; Cordeiro, Yraima; Caughey, Byron et al. (2014) Heparin binding confers prion stability and impairs its aggregation. FASEB J 28:2667-76
Hopping, Gene; Kellock, Jackson; Barnwal, Ravi Pratap et al. (2014) Designed ?-sheet peptides inhibit amyloid formation by targeting toxic oligomers. Elife 3:e01681
Sim, Valerie L; Caughey, Byron (2009) Recent advances in prion chemotherapeutics. Infect Disord Drug Targets 9:81-91